Type D simian retroviruses (SRV) are exogenous D type oncorna viruses that are the most significant cause of endemic acquired immunodeficiency syndrome (AIDS) in biomedical research colonies of macaques. Five serogroups of SRVs have been identified; however, only members of serogroups 1, 2 and 3 have been cloned and sequenced. Only members of serogroup 2 have been identified in wild macaque populations and the natural host of the other serogroups is not known. Serogroup 3 viruses have been recovered from humans but have been considered contaminants. Serogroup 5 contains a single prototype virus, D5/RHE/OR, isolated from a rhesus macaque imported to the ORPRC from the Peoples' Republic of China. This isolate produces severe immunodeficiency when transmitted to naive juvenile rhesus macaques. Serologic and hybridization studies suggest that SRV-5 is distinct from other serogroup members. We have sequenced the env and gag genes of a D5/RHE/OR infectious molecular clone. The D5/RHE/OR env polyprotein is 592 amino acid residues in length (gp70 and gp20 molecules are 400 and 192 amino acid residues, respectively), and contains 12 Asn-X-Ser(Thr) glycosylation sites, 11 of which are found within gp70. The D5/RHE/OR gp70 and gp20 molecules are 59.3 - 61.8% (range) and 83.9 - 84.4% (range) similar, respectively, to corresponding env glycoproteins identified for serogroups 1, 2 and 3. Interestingly, the D5/RHE/OR gp70 molecule is the largest among previously identified SRV serogroups (400 amino acid residues versus 388, 394 and 395 amino acid residues for D2/CEL/OR, Mason-Pfizer Monkey Virus (MPMV), and D1/RHE/CA, respectively). In the D5/RHE/OR gag polyprotein, proteins p10 and p27 (100 and 226 amino acid residues, respectively) are identical in length to those identified for serogroups 1, 2 and 3, while the lengths of p14, p4, p12 and p24 (94, 36, 82 and 63 amino acids, respectively) differ from those found in the other serogroups by one amino acid. The D5/RHE/OR gag region that is least conserved is p24; this region is 57.1%, 49.2% and 57.1% similar (at the amino acid level) to corresponding proteins found in D1/RHE/CA, D2/CEL/OR and MPMV, respectively. The D5/RHE/OR gag region that appears most conserved is p27, with 97.3%, 95.1% and 96.5% amino acid similarity for serogroups 1, 2 and 3, respectively. Sequencing the complete D5/RHE/OR genome will provide further insight into the genetic diversity of type D SRVs and may provide the beginning framework for understanding the molecular basis for serogroup differences in simian acquired immunodeficiency and phylogenetic studies.